Inheritance, mode of inheritance, and candidate genes for primary hyperparathyroidism in Keeshonden

BACKGROUND: Primary hyperparathyroidism (PHPT) is caused by inappropriate secretion of parathyroid hormone (PTH) by autonomously functioning neoplastic or hyperplastic parathyroid "chief" cells. Keeshonden are thought to be over-represented in studies on canine PHPT, but no proof of heritability or mode of inheritance has been published. The canine disease clinically resembles human familial isolated hyperparathyroidism (FIHP). HYPOTHESIS: Primary hyperparathyroidism in Keeshonden is genetically transmitted and is caused by a mutation in 1 of 4 genes implicated in human FIHP: MEN1, CASR, HRPT2, or RET. ANIMALS: Pedigrees consisting of 1647 Keeshonden were created including 219 Keeshonden with known PHPT phenotypes (69 positive). DNA samples were obtained from 176 of the 219 Keeshonden (34 positive). METHODS: Heritability and mode of inheritance were determined by segregation analysis. Canine homologs to the human genes were identified. Exons and surrounding intron regions were sequenced and scanned for sense-altering polymorphisms or polymorphisms that segregated with the disease. Messenger RNA from a parathyroid tumor of an affected Keeshond was analyzed for polymorphisms and splice alterations. RESULTS: PHPT follows an autosomal dominant mode of inheritance in Keeshonden with possible age-dependent penetrance. No polymorphisms identified in the genes analyzed were associated with a change in predicted protein or in hypothesized splice sites. CONCLUSIONS AND CLINICAL IMPORTANCE: PHPT is an autosomal dominant, genetically transmitted disease in Keeshonden. Once the mutation locus is identified, genetic testing should quickly decrease the incidence of PHPT in this breed. It is unlikely that mutations in MEN1, CASR, HRPT2, or RET cause PHPT in Keeshonden.     

Expression of interleukin-1beta in the digital laminae of horses in the prodromal stage of experimentally induced laminitis

OBJECTIVE: To study expression of interleukin-1beta (IL-1beta) in the digital laminae of horses in the prodromal stage of experimentally induced laminitis. ANIMALS: 8 healthy adult horses with no signs of laminitis. PROCEDURES: Black walnut extract was administered via nasogastric tube to 4 horses, and water was administered to the remaining 4 (controls). Complete blood counts and physical examinations were performed every 30 minutes after administration of black walnut extract or water. General anesthesia was induced when total WBC count decreased by 30% in horses given the black walnut extract and 3 hours after water administration in control horses. The left forefoot was perfusion fixed with neutral-buffered 10% formalin, and paraffin-embedded sections of the digit were used for in situ hybridization with an equine-specific IL-1beta probe. RESULTS: IL-1beta mRNA expression was observed in perivascular cells of the small laminar venules and capillaries in all 4 horses given black walnut extract and in interstitial cells remote from the microvasculature in 1 of the 4. Other cellular components of the laminar tissue and cellular components of the digital arterioles and veins did not exhibit IL-1beta mRNA expression. Expression of IL-1beta mRNA was not detected in laminae from control horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IL-1beta mRNA is expressed by perivascular cells in the laminar tissues of horses in the prodromal stage of experimentally induced laminitis. This provides evidence of an inflammatory process during the prodromal stage of laminitis, indicating that local digital proinflammatory cytokine expression may be an initiating factor in laminitis.     

Studies on canine pregnancy using B-mode ultrasound: Development of the conceptus and determination of gestational age

Development of the conceptus was characterised using B-mode ultrasound in a standard size of dog (labrador retrievers, golden retrievers and their crosses; weight range 22 to 30 kg). Growth curves were established for various measurements of the conceptuses. Regression equations allowed the prediction of the expected time of parturition. Multiple regression analysis of two measurements (biparietal diameter and trunk diameter) resulted in an increase in the confidence of prediction.     

Developmental comparisons of boars and barrows: II. Body composition and bone development

Differences in total carcass bone, muscle and fat, and linear measurements of the tibia and radius were evaluated in barrows at 105 kg and boars at 105, 118, 132 and 145 kg live body weight. The carcasses of five replicates were physically separated into skin, bone and soft tissues, and the linear measurements of the tibia and radius were obtained on seven replicates. At live weight of 105 kg, boars did not differ significantly in fat-free muscle, but they had 33.2% less fat, 11% greater bone weight and 14% greater skin weight than barrows. At 145 kg, boars had total carcass fat weight comparable with 105-kg barrows. Fat-free muscle, bone and skin weight of boars increased at linear rates of .41, .083 and .104 kg/kg of body weight increase from 105 to 145 kg, respectively. At 105 kg, density and length of the tibia and radius did not differ between boars and barrows. The tibia of boars were heavier than those of barrows at 105 kg, resulting in a greater ratio of tibia weight to length (indirect measure of bone thickness). As boars increased in live weight from 105 to 145 kg, total weight and length of the tibia and radius increased linearly. The ratio of weight to length of the tibia and radius increased during this 40-kg weight gain, indicating that weight of both bones increased at a greater rate than length. These results indicate that boars and barrows have the same weight of total carcass fat when boars are 40 kg heavier than the barrows. The greater bone weight of boar carcasses compared with barrows is due to greater bone thickness.     

Effects of aspirin and propranolol alone and in combination on hemostatic determinants in the healthy cat

The effects of aspirin (75 mg orally/average-size cat) and propranolol (5 mg orally every 8 hours/average-size cat) alone and in combination on hemostatic determinants in healthy cats were studied. In cats, aspirin alone did not cause a significant effect in platelet numbers, plasma fibrinogen, activated partial thromboblastin time, prothrombin time, thrombin time, or platelet aggregation response to adenosine diphosphate. Aspirin did, however, significantly reduce the degree of aggregation induced by acid soluble collagen. Propranolol alone or in combination with aspirin did not cause a significant effect on platelet numbers, plasma fibrinogen, activated partial thromboblastin time, prothrombin time, thrombin time, or platelet aggregation in response to acid soluble collagen, adenosine diphosphate, or adrenaline. It was concluded that aspirin alone at the recommended dosage of one-quarter of a 5-grain tablet (1.25 grains or 75 mg) every other day will significantly affect platelet function and may be of value in the prevention of thromboembolic disease in the cat.     

Developmental orthopaedic disease and early osteoarthritis of the temporomandibular joint in a 15-month-old Quarter Horse filly

A 15-month-old Quarter Horse filly presented for evaluation of hard swellings over the left temporomandibular joint (TMJ) and the right metatarsophalangeal joint (MTPJ). The TMJ swelling had been noted since she was weaned at 4 months of age and had slowly enlarged since then. Radiographs of both TMJs and the right MTPJ were performed, which revealed severe osteoarthrosis associated with osteochondrosis-like lesions. The filly was subjected to euthanasia due to the poor prognosis for performance. Computed tomography and post-mortem examination, including histopathology of the left TMJ, revealed early osteoarthritis (OA) associated with osteochondrosis-like lesions of the left TMJ and the right MTPJ, while the right hind proximal interphalangeal joint (PIPJ) was diagnosed with early OA.